Topical
Tacrolimus Is An Effective Alternative to Steroids for Eczema

Question

A 40-year-old male brings his two sons to see
you in clinic, ages 6 and 7 with moderately severe eczema. Both have
had moderately successful courses with corticosteroids in the past,
but he wants to know if there is any other treatment you would prescribe
for his sons. In children with moderately severe eczema, is topical
tacrolimus more effective than steroids?

Other studies have demonstrated long-term safety in adults, but
such studies are still ongoing in children.

NNT for an observed response: 3 patients for two weeks.

Summary of Key Evidence

180 children between the ages of 7 and 16 with 5 to 30 % body
surface area involvement of atopic dermatitis were randomized
to receive twice a day applications of either tacrolimus ointment
at 1 of 3 concentrations-0.03 % (n=43), 0.1% ( n=49), 0.3% (n=44),
or vehicle (propylene carbonate, white wax, mineral oil, and petrolatum)
for 22 days with a two week follow up period.1

Patients had to stop topical corticosteroids for one week, and
systemic corticosteroids for six weeks. Patients receiving immunotherapy
or phototherapy had to stop at least one month before enrollment.

Patients were randomized to one of the four treatment arms. The
study was blinded-all tubes of medication looked the same.

Eighteen of the 180 patients discontinued treatment early; 7 in
the vehicle group, 2 in 0.03% tacrolimus group, 5 in the 0.1%
group, and 4 in the 0.3 % group. 4 of the 7 patients in the vehicle
group and one patient in the tacrolimus group discontinued treatment
because of perceived lack of efficacy, 2 of 44 and 5 of 136 discontinued
treatment because of adverse events and noncompliance accounted
for 1 patient in the vehicle group and 5 in the tacrolimus groups.

Outcomes were assessed by the Physicians' Global evaluation of
clinical response, modified Eczema Severity Index, Head and Neck
Total Score, and patient's assessment to overall treatment.

Blood levels monitored on days 0, 4 and 22. Highest level noted
was 2.66 ng/ml, most under 1 ng/ml.

Using the Physicians' Global Evaluation of Clinical Response (greater
than 75 % improvement), 69% CI 53-82% (0.03%), 67% CI 52-81% (0.1%),
70% CI 54-83% (0.3%), and 38% CI 24-54 (vehicle) reported a response.
Estimating the control event rate at 62% (those that did not see
a response in the vehicle group), the EER is 30%, the RRR 52%
with a ARR of 32% and NNT of 3.

Additional
Comments

Tacrolimus is thought to
act by penetrating cells, binding to cellular proteins (FK-binding proteins)
which block the action of calcineurin, which in turn results in a suppression
of cytokine gene transcription.

Atopic dermatitis is the
most common chronic skin condition in children--10% of the pediatric
age population have it.

Tacrolimus is less than
0.5% systemically absorbed

Most of the adverse effects
(burning) were described at the beginning of therapy with denuded skin.
There were no systemic adverse events.

The youngest participant
in this study was 7 years old. We don't know how this would work for
younger children.

While the price of topical
tacrolimus has not been set, it will likely be expensive compared with
steroid treatments.